Kidneys ammonium excretion

Amino groups released by deamination reactions form ammonium ion (NH " ), which must not escape into the peripheral blood. An elevated concentration of ammonium ion in the blood, hyperammonemia, has toxic effects in the brain (cerebral edema, convulsions, coma, and death). Most tissues add excess nitrogen to the blood as glutamine. Muscle sends nitrogen to the liver as alanine and smaller quantities of other amino acids, in addition to glutamine. Figure I-17-1 summarizes the flow of nitrogen from tissues to either the liver or kidney for excretion. The reactions catalyzed by four major enzymes or classes of enzymes involved in this process are summarized in Table T17-1. 

In aquatic animals, ammonia diffuses out of the body through the skin, but land animals excrete excess ammonia either as urea or uric acid. Ammonia is excreted by humans on high meat diets as a strategy to conserve Na+ and K +. Excess PO4- and SO4- produced from phosphoproteins and S-containing amino acids are excreted as ammonium salts Na+ and K+ are exchanged for NH in the kidney. The excretion of urea requires a plentiful supply of water, as it is normally excreted in solution, whereas uric acid is very insoluble and is excreted as a solid by birds and reptiles. Thus, in animals in which weight, or the conservation of water, is important (e.g., birds), excess ammonia is excreted as uric acid. 

The kidney plays a major role in the maintenance of acid-base homeostasis, particiilarly with respect to metabolic acidosis. In response to metabolic acidosis, the kidney is able to increase its production of ammonia resulting in enhanced urinary ammonium excretion, a process linked to proton excretion and the generation of... 

Some of the metabolic changes in the kidney in such experiments are known. Sodium is temporarily depleted, and then ammonium excretion is markedly increased. The increased excretion of ammonium ions is accompanied by de novo synthesis of glutaminase. Although the adaptation just described can be expected, other metabolic changes observed in the kidney of animals made acidotic experimentally are somewhat more difficult to understand. They include increased activity of the enzymes of the hexose monophosphate shunt, increased rates of gluconeogenesis and lipogenesis, and compensatory hypertrophy of the kidney, somewhat reminiscent of that observed after unilateral nephrectomy [48]. 

As described above, some of the H ions produced in the course of metabolism are converted to NH4 in the kidney and excreted in the form of ammonium salts. The output of ammonia in this form is usually about 0-5-1 0 g per day but this is increased in acidosis. 

Describe how the kidney can excrete large amounts of acid or alkali without producing urine whose pH varies outside the limits of 4.5 to 7.8. Include the role of phosphates and of ammonium. 

This is a measure of the renal excretion of hydrogen ions. It can be determined by measuring the amount of alkali required to titrate a fixed volume of the urine to pH 7.4. Titratable acidity is increased when acid-forming foods have been taken and in some acidotic conditions, such as diabetic ketoacidosis when keto acids are excreted in the urine. Titratable acidity can also be measured in the ammonium chloride loading test (q.v.), a procedure designed to test the ability of the kidneys to excrete an acid load. 

Diquat and paraquat are quaternary ammonium compounds largely used as contact herbicides and crop desiccants. When systemic absorption occurs, paraquat and diquat are rapidly distributed into the body. Paraquat primarily accumulates in the lungs and kidneys, while the highest diquat concentrations have been found in the gastrointestinal tract, liver, and kidneys (WHO, 1984). Urine is the principal route of excretion for both diquat and paraquat, which are primarily eliminated as unmodified compounds. Occupationally exposed workers can be monitored by measuring paraquat and diquat concentrations in urine samples (Table 6). Blood concentrations are useful to monitor acute poisoning cases. 

Rabbits form bicarbonate in the gut and absorb it. They do not have to form new bicarbonate in the kidneys and need not excrete ammonium ions in the urine, but they still need to excrete organic anions. These organic anions are accompanied in the urine by sodium or potassium ions, which can generate a severe negative sodium balance for the period that the rabbits are on a browse diet(Iason and Palo, 1991). Therefore, lagomorphs excrete biotransformational... 

Ammonia can diffuse freely into the urine through the tubule membrane, while the ammonium ions that are formed in the urine are charged and can no longer return to the cell. Acidic urine therefore promotes ammonia excretion, which is normally 30-50 mmol per day. In metabolic acidosis (e.g., during fasting or in diabetes mellitus), after a certain time increased induction of glutaminase occurs in the kidneys, resulting in increased NH3 excretion. This in turn promotes H"" release and thus counteracts the acidosis. By contrast, when the plasma pH value shifts towards alkaline values alkalosis), renal excretion of ammonia is reduced. 

Ammonia (NH3) and the ammonium ion (NH4"1") are highly toxic to mammalian cells. In vivo, ammonium is secreted by the cells and transported to the mitochondria of hepatocytes, where it is converted into urea via the urea cycle. Urea production occurs almost exclusively in the liver and is the fate of most of the ammonium channeled there. The urea passes into the bloodstream and thus to the kidneys and is excreted into the urine. Mammalian cells in culture secrete ammonium into the culture medium, where its concentration increases gradually because there is no ammonium recycling pathway (Newland et al., 1990). 

The effect of urinary pH on drug ionization also has toxicological implications. For example, in cases of phenobarbital (a weak acid barbiturate) overdose the urine can be alkalinized (the pH elevated) by administering sodium bicarbonate to the patient. The resultant increase in pH shifts the dissociation equilibrium for this weak acid to the right, producing an increase in the proportion of the ionized form, less reabsorption in the kidneys, and more rapid elimination. Conversely, acidifying the urine with ammonium chloride will increase the excretion rate of drugs that are weak bases since they will be more protonated (ionized) and less reabsorbed (more polar, less lipophilic). 

When ammonia enters the body, it is converted to urea and excreted by the kidneys. The capacity for detoxification via urea is sufficient to eliminate the ammonium ion when ammonia is inhaled in non-irritating concentrations. Repeated inhalation can cause a higher tolerance because the mucous membranes become increasingly resistant. Ammonia is not considered to be carcinogenic nor is it mutagenic. The effects of different ammonia concentrations are summarized in Table 8.374. 

When absorbed into the systemic circulation, ammonia is primarily excreted by the kidney as urea and urinary ammonium compounds (Gay et al. 1969 Pitts 1971). Absorbed ammonia also can be excreted as urea in feces (Richards et al. 1975) and as a perspiration constituent (Guyton 1981 Wands 1981). In a study of male subjects exposed to ammonia at concentrations up to 500 ppm for 30 min, Silverman et al. (1949) found that 70-80% of inhaled ammonia was excreted in expired air. Ammonia in expired air returned to normal concentrations within 3 to 8 min after exposure was stopped. The investigators calculated that if all the retained ammonia were absorbed into the blood, there would be no significant change in blood or urine urea, ammonia, or nonprotein nitrogen. 

The glutamine synthase reaction is important in several respects. First, it produces glutamine, one of the 20 major amino acids. Second, in animals, glutamine is the major amino acid found in the circulatory system. Its role is to carry ammonia to and from various tissues, but principally from peripheral tissues to the kidney, where the amide nitrogen is hydrolysed by the enzyme glutaminase (reaction below) this process regenerates glutamate and free ammonium ion, which is excreted in the urine. 

FJGURE, 20 Eliminiitian of ammonium ions via the urea cycle or via direct excretion. With protein catabolism, the excretion of wafste nitrogen via the urea cycle results in net prod union of acid in the body however, excretion of ammonium ions by the kidney into the urine does not result in this production of acid in the body. 

The belladonna alkaloids are absorbed rapidly after oral administration (75). They enter the circulation when applied locally to the mucosal surfaces of the body. Atropine absorbed from inhaled smoke of medicated cigarettes can abolish the effects of intravenous infusion of methacholine in humans. The transconjunctival absorption of atropine is considerable. About 95% of radioactive atropine is absorbed and excreted followingsubconjunctival injection in the rabbit. The total absorption of quaternary ammonium derivatives (Section 3.5) of the alkaloids after an oral dose is only about 25%. The liver, kidney, lung, and pancreas are the most important organs that take up the labeled atropine. The liver probably excretes metabolic products of atropine by way of bile into the intestine (in mice and rats). 

Ammonia arises in the body principally from the oxidative deamination of amino acids. In addition to its uptake in the reactions mentioned above, ammonia is also excreted in the urine as ammonium salts. This is not derived directly from the blood ammonia but is formed by the kidney from glutamine by the action of glutaminase. In metabolic acidosis, ammonia production and excretion by the kidney is greatly increased, and conversely it is decreased in metabolic alkalosis. This may be an important means of excreting excess ammonia. It must be remembered that ammonia formed by the action of intestinal bacteria on the protein hydrolyzates in the intestine can be also absorbed. The contribution of the ammonia formed in this way to the total ammonia in the body is unknown. Since this ammonia drains into the portal circulation, it is promptly removed by the liver. 

Last, ammonia is excreted in the urine in the form of ammonium salts. Normally, however, this is relatively small, but it may be increased in metabolic acidosis, if kidney tubular function is normal. Ammonia is synthesized from glutamine by the kidney as required in order to conserve fixed base, e.g., sodium or potassium or to neutralize excessive amounts of acid excreted in the urine as, for example, in acidosis. 

Since vanadium is poorly absorbed in the gastrointestinal tract, a large percentage of vanadium is excreted unabsorbed in the feces in rats following oral exposure. More than 80% of the administered dose of ammonium metavanadate accumulated in the feces after 6 days (Patterson et al. 1986). After 2 weeks of exposure, 59.1 18.8% of sodium metavanadate was found in the feces (Bogden et al. 1982). However, the principal route of excretion of the small absorbed portion of vanadium is through the kidney in animals. 

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